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In vitro concentration response studies and in vitro phase II tests as the experimental basis for regional chemotherapeutic protocols

✍ Scribed by Karl-Heinz Link; Gerd Leder; Jürgen Pillasch; Urwe Butzer; Ludger Staib; Marko Kornmann; Uwe Bruckner; Hans Günther Beger


Publisher
John Wiley and Sons
Year
1998
Tongue
English
Weight
184 KB
Volume
14
Category
Article
ISSN
8756-0437

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✦ Synopsis


The theoretical pharmacologic benefit of regional vs. systemic chemotherapy is defined and the concentration response behavior of cytostatic drugs and their optimal exposure times are described with human cancer cell lines (HT29, NMG64/84) and fresh human tumor cell suspensions in the human tumor colony assay (HTCA). The theoretical pharmacological advantages are 5.8 to 6 for adriamycin (ADM), 8 for cisplatinum (CDDP), 6.3 for epidoxorubicin (EPI), 22 to 58 for 5-fluorouracil (5FU), 4.6 for mitomycin C (MMC), and 6.3 for mitoxantrone (NOV). The drugs differed in their cytotoxic potency in vitro and thus also potential efficacy for regional chemotherapy; however, all but 5-fluorodeoxyuridine (5FUDR) exerted cytotoxicity dependent on exposure time and concentration. On average, elevation of the test concentrations by 1 lg doubled responses in fresh human tumor cell suspensions. From these results and clinical considerations, optimal times were defined for the regional chemotherapy strategies of hepatic artery infusion, intraperitoneal instillation, and chemoembolisation as performed at our institution.